title: The serine-threonine kinase inositol-requiring enzyme 1α (IRE1α) promotes IL-4 production in T helper cells.
abstract: The inositol-requiring enzyme 1α (IRE1α) is a serine-threonine kinase that plays crucial roles in activating the unfolded protein response. Studies suggest that IRE1α is activated during thymic T cell development and in effector CD8(+) T cells. However, its role in regulating T helper cell differentiation remains unknown. We find that IRE1α is up-regulated and activated upon CD4(+) T cell activation and plays an important role in promoting cytokine IL-4 production. CD4(+) T cells from IRE1α KO mice have reduced IL-4 protein expression, and this impaired IL-4 production is not due to the altered expression of Th2 lineage-specific transcription factors, such as GATA3. Instead, IL-4 mRNA stability is reduced in IRE1α KO T cells. Furthermore, treatment of T cells with an IRE1α-specific inhibitor, 4μ8C, leads to a block in IL-4, IL-5, and IL-13 production, confirming the role of IRE1α in the regulation of IL-4. This study identifies a regulatory function for IRE1α in the promotion of IL-4 in T cells.
authors.affiliation: From the Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611.
authors.forename: Kyeorda L
authors.initials: KL
authors.lastname: Kemp
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lin
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.forename: Beixue
authors.initials: B
authors.lastname: Gao
authors.forename: Jianxun
authors.initials: J
authors.lastname: Song
authors.forename: Kezhong
authors.initials: K
authors.lastname: Zhang
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D004722:Endoribonucleases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: Cytokine; ER Stress; IL-4; IRE1; Lymphocyte; Signal Transduction; T Cell Biology; T Cell Differentiation